Diana received her B.A. in Biochemistry from the University of Pennsylvania, and then a Ph.D. in Cell Biology and Genetics from Cornell. Now she is a freelance science writer and editor in White Plains, New York. Her son was diagnosed with celiac disease in 2006, at the age of five, and she has been keeping her family healthy by feeding them gluten free treats ever since.

By Diana Gitig Ph.D.

Published on 05/27/2011

The more severe form of Refractory Celiac Disease, RCDII, might be more common in Europe than in the US.

Celiac.com 05/27/2011 - Refractory Celiac Disease (RCD) is exactly what it sounds like: persistent malabsorption symptoms and intestinal villous atrophy even after following a gluten free diet. It is divided into two subtypes. RCDI has normal intraepithelial lymphocytes (IELs) while RCDII has abnormal IELs. RCDII is by far the more severe - there is no effective treatment, and it is often fatal within five years. Recent studies in Amsterdam and Paris have reported that RCDII can account for 28-75% of RCD patients. A group of researchers led by Ciaran Kelly at the Celiac Center at Beth Israel Deaconess Medical Center in Boston, the only specialized celiac center in New England, set out to determine if the same was true in the United States. They found a much lower incidence, 17%, of RCD patients with RCDII.

An editorial by Malamut and Cellier accompanying Kelly's report in the American Journal of Gastroenterology suggests a number of factors that could account for the difference. Primary among them is the different methodology used to diagnose RCDII. In the US study only one method, immunohistochemistry, was used to ascertain whether the IELs were normal or not; in Europe they used three independent experimental techniques to confirm this data. The American researchers note that if they had in fact underdiagnosed RCDII they should have seen more severe cases of RCDI, and they did not. Malamut and Cellier point out that the Boston study may also have overdiagnosed RCDI by examining biopsy samples done only six months after institution of a gluten free diet, when villous atrophy may not have completely healed. An inflated number of RCDI cases would generate an erroneously low percentage of RCDII cases. But the Americans note that only four of the thirty-four cases of RCD they examined were from patients who had been on a gluten free diet for less than a year.

Alternatively, the relative dearth of RCDII cases in the US as compared to Europe could be attributed to the different genetic backgrounds of the populations involved - the "melting pot" present in the US rather than the older stocks that may be in Europe. It has been reported that RCDII correlates with HLA-DQ2 homozygosity, and in fact, the HLA-DQ8 allele was found to be more common in celiac patients in New York than in those in Paris. It is also possible that an environmental factor, such as the amount or type of gluten consumed before diagnosis, could account for the discrepancy, but this remains to be investigated. Therapeutic options for the aggressive RCDII are still severely limited; research into it should certainly continue, on both continents.

Sources:

Roshan et al. The Incidence and Clinical Spectrum of Refractory Celiac Disease in a North American Referral Center. The American Journal of Gastroenterology 2011; 106: 923-928.